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CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist’s sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2’- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2’- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1 . On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1 .

Micro-RNAs (mi-RNAs) can regulate various tumor suppressor genes or oncogenes thus they were monitored in various types of cell carcinoma. Lung cancer extensive progress has led not only to understanding the molecular pathways governing human lung cancer, but it has also created a vast reservoir for alternative development of novel liposomal Nano-medicines counteracting this malignancy. Liposomal drug delivery system can passively accrue in cancer cells via the retention phenomenon and enhanced permeability. This article highlighted liposomal-loaded nano-medicine as a potential treatment for lung cancer and clarifies the correlated miRNA and mRNA gene profile. Lung cancer was induced experimentally in rats via 3-methylcholanthrene (3-MCA) in a dose of 40 mg IV for 4 months followed by treatment via certain liposomal-loaded compounds, namely, liposomal doxorubicin (LIP-DOX), curcumin (LIP-CUR) and glutathione (LIP-GSH) in a dose of 5mg/kg IP daily for 1 month and were compared with their non-liposomal analogue. Concomitant supplementation with the aforementioned liposomal-loaded compounds impact on lung cancer was estimated via monitoring microRNA biomarkers including miR-122-5P and SNORD-78, pro-inflammatory biomarker Survivin, apoptotic and cell survival biomarkers including fms-related tyrosine kinase 3 (FLT-3), jasnus Janus kinase-2 (JAK-2), Phosphatidylinositol-3-kinase (PI3K), serine–threonine protein kinase (AKT) and tumor suppressor protein (P53). Liposomal-loaded doxorubicin, curcumin and glutathione significantly modulated these previously deviated genes as compared with their non-liposomal analogue, in addition to modulating lipid peroxide (LPOO) and total antioxidant capacity (TAC). MiR-122-5P and SNORD-78 were also amended reflecting the prospective impact of liposomal-loaded-nano-medicine on lung cancer treatment via up regulating P53 and down regulating PI3K/AKT/JAK2/FLT3 signaling pathway.

Different environmental toxins especially heavy metals exist in soil, water, and air recording toxic effect on human, animal, and plant. These toxicant elements are widespread in environment causing various disturbances in biological systems. Numerous strategies have been applied recently to alleviate heavy metal contamination; however, most of these strategies were costly and seemed unfriendly to our environment. Probiotics are living cell bacteria with beneficial characteristics for human health. Lactobacillus and Bifidobacterium are the major probiotic groups; however, Pediococcus, Lactococcus, Bacillus, and yeasts are recorded as probiotic. The vital role of the probiotics on maintenance of body health was previously investigated. Probiotics were previously recorded to its powerful capacity to bind numerous targets and eliminate them with feces. These targets may be aluminum, cadmium, lead, or arsenic. The current review discusses the history of probiotics, detoxification role of probiotics caused by heavy metals, and mechanism of their action that modulate different signaling pathway disturbance associated with heavy metal accumulation in biological system.

Methotrexate (MX), a competitive inhibitor of dihydrofolate reductase, can inhibit DNA and RNA production and is a powerful anticancer agent widely utilized in clinical practice for treating nonneoplastic maladies, as psoriasis and rheumatoid arthritis; meanwhile, its probable prescription dose and interval of administration are strictly limited due to dose-related organ damage. Former studies verified that kidney, brain, liver, and lung harms are prospective obstacles of methotrexate administration. To understand the machinery of methotrexate-prompt toxicity, various mechanisms were investigated. The former is an autophagy defense mechanism; autophagy is a self-digesting mechanism responsible for the removal of damaged organelles and malformed proteins by lysosome. The contemporary article hypothesized that turmeric or its liposomal analog could defeat autophagy of MX-induced acute toxicity. Methotrexate, in a dose of 1.5 mg/kg, was administered intravenously followed by turmeric and liposomal turmeric treatment in a dose of 5 mg/kg for 30 days in rats. Increment in autophagy (AUTP) consent by MX administration was attenuated by concurrent treatment via turmeric and liposomal turmeric that was reliable on the alteration in apoptotic markers. The assembly of FOXO-3 in serum post methotrexate administration was suppressed by concurrent treatment via liposomal turmeric. Apoptosis/autophagic marker investigation was evaluated through the gene expression of Bax (BCL2-associated X protein)/Bcl2 (B-cell lymphoma 2)/P53 (tumor protein P53)/SiRT-1 (sirtuin silent mating-type information regulation 2 homolog 1) and FOXO-3 (forkhead box transcription factor-3)/ERDJ-4 (endoplasmic reticulum localized DnaJ homologs)/BNP (brain natriuretic peptide B) signaling. The cell death of all cells was categorized to achieve autophagy. Interestingly, Bax/Bcl2/P53/SiRT-1 signaling pathways were downregulated, contributing to inhibiting the initiation of autophagy. Meanwhile, FOXO-3/BNP/ERDJ-4 reduction-implicated noncanonical autophagy pathways were involved in methotrexate-induced autophagy, whereas this change was suppressed when turmeric was administered in liposomal form. These outcomes recommended that liposomal turmeric prevents MX-induced acute toxicity through its autophagy, antioxidant, and antiapoptotic properties.

Background and ObjectivesNanoparticle (NP) drug delivery systems have been developed recently to resolve the obstacle of drug resistance, contributing to the effective drug delivery to the target organ. A comparative study was carried out herein between doxorubicin (DOX), doxorubicin-loaded titanium NPs, DOX-loaded lactoferrin NPs, DOX-NPs, and PEGylated-doxorubicin (PEG-DOX) on the reno-carcinogenic impact of 3-methylcholanthrene (CA).MethodsIn-vivo models were exposed to CA at a dose of 50 mg/kg body weight and left for 3 months till the incidence of chronic kidney disease, followed by one month of treatment with the aforementioned nanomedicines.ResultsCA downregulated DOX resistance biomarkers, including the gene expression of KRAS, FKBP5, P53, and JAK2, and the kidney tumor marker arginase II. In addition, CA increased the levels of the kidney biomarkers creatinine and urea as well as the minerals chloride and magnesium. Decreased gene expression of FKBP5, KRAS, P53, and JAK2 was reversed after the treatment with DOX-loaded titanium NPs, DOX-NPs, DOX-loaded lactoferrin NPs, and PEG-DOX. PEG-DOX abolished the detrimental effects of CA via upregulating the gene expression of the immunophilin protein (FKBP5), the oncogene (KRAS), the tumor suppressor gene (P53), and JAK2, which indicate DOX drug resistance via regulating cell differentiation, division and apoptosis.ConclusionPEG-DOX restored renal function and resolved DOX resistance via KRAS, FKBP5, P53, and JAK2 signaling pathways manipulation; consequently, PEG-DOX may provide a useful adjunct treatment for chronic kidney disease.

Background and objectiveBone marrow-derived mesenchymal stem cells (MSCs), possess the unique ability of self-renewal and development into specialized cells, and long-lived cells with specific metabolic needs. It has been demonstrated that autophagy is essential for MSC differentiation, quiescence, activation, and self-renewal. The present study aims to elucidate how autophagy influences bone marrow-derived MSC post-novodrin-prompted liver dysfunction.MethodsHepatic dysfunction was induced in rats using novodrin (100 mg/kg, subcutaneously), which was divided into two doses for two alternative days, followed by the treatment with 100 µL of intravenous injection of allogeneic MSCs (5 × 106).ResultsA month preceding MSC therapy, a marked decline in liver function biomarkers, including alanine aminotransferase and aspartate aminotransferase, was observed, in addition to the significant decrease in oxidative stress biomarker, lipid peroxide. Meanwhile, novodrin significantly elevated the gene expression of cell survival biomarkers, including signal transducer and activator of transcription, phosphatidylinositol-3-kinase, and serine/threonine kinase-1, in addition to the concomitant increase in oncogenic biomarker, phosphatase and tensin homolog, and this was reversed post-MSC implantation. Furthermore, the autophagy biomarkers, including Beclin-1 and X-box binding protein 1, were restored post-MSC implantation. Moreover, the MSCs labeled with the PKH26 red fluorescent dye were sown into the injured liver tissue, which presented with hepatic tissues with a nearly normal architecture as confirmed through histopathological examination.ConclusionThe present study demonstrated that autophagy is essential for bone marrow-derived MSC in novodrin-induced liver dysfunction.

A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC50 value of 0.375 µg/ml. Mechanistic studies revealed the potential of GMann to arrest cell cycle at G2/M phase with induction of apoptosis. Biochemical results in vivo showed a significant reduction in serum transaminases (ALT and AST) as well as hepatic malondialdehyde (MDA) and nitric oxide (NOx). Molecular analysis declared a significant down-regulation in mRNA gene expression of both nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF-α). Furthermore, a significant down-regulation in the cellular oncogene-fos (C-fos) and marked up-regulation in Glycogen synthase kinase-3 (GSK-3β) level were observed. These results were supported with histopathological investigation. Whereas GMann improved inflammatory and apoptotic markers, it could be a promising new therapeutic agent for HCC suppression and this warrant further development as a possible drug candidate for HCC.

Hepatocellular carcinoma (HCC) is among the common cancers, but difficult to diagnose and treat. l-asparaginase has been introduced in the treatment protocol of pediatric acute lymphoblastic leukemia (ALL) since the 1960s with a good outcome and increased survival rates to nearly 90%. Moreover, it has been found to have therapeutic potential in solid tumors. Production of glutaminase-free-l-asparaginase is of interest to avoid glutaminase-related toxicity and hypersensitivity. In the current study, an extracellular l-asparaginase that is free of l-glutaminase was purified from the culture filtrate of an endophytic fungus Trichoderma viride. The cytotoxic effect of the purified enzyme was evaluated in vitro against a panel of human tumor cell lines and in vivo against male Wister albino mice intraperitoneally injected with diethyl nitrosamine (200 mg/kg bw), followed by (after 2 weeks) oral administration of carbon tetrachloride (2 mL/kg bw). This dose was repeated for 2 months, and after that, the blood samples were collected to estimate hepatic and renal injury markers, lipid profiles, and oxidative stress parameters. l-asparaginase was purified from T. viride culture filtrate with 36 purification folds, 688.1 U/mg specific activity, and 38.9% yield. The highest antiproliferative activity of the purified enzyme was observed against the hepatocellular carcinoma (Hep-G2) cell line, with an IC.sub.50 of 21.2 g/mL, which was higher than that observed for MCF-7 (IC.sub.50 34.2 g/mL). Comparing the DENA-intoxicated group to the negative control group, it can be demonstrated that l-asparaginase adjusted the levels of the liver function enzymes and the hepatic injury markers that had previously changed with DENA intoxication. DENA causes kidney dysfunction and altered serum albumin and creatinine levels as well. Administration of l-asparaginase was found to improve the levels of the tested biomarkers including kidney and liver function tests. l-asparaginase treatment of the DENA-intoxicated group resulted in a significant improvement in the liver and kidney tissues to near normal similar to the healthy control group. The results suggest that this purified T. viridel-asparaginase may be able to delay the development of liver cancer and may be used as a potential candidate for future application in medicine as an anticancer medication.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h). Four weeks post-MSCs transplantation and digoxin treatment a significant reduction in serum cardiac markers, aspartate aminotransferase, creatine kinase-MB and troponine II was observed. Meanwhile, isoproterenol significantly reduced the gene and protein expression of the oxidative stress marker nuclear-related factor-2 (Nrf2) with a concomitant elevation in (MDA) level and inflammatory markers toll-like receptor-4 (TLR-4), intercellular adhesion molecules (ICAMs) and (VCAM-1). Moreover, apoptotic marker (P53) was significantly down-regulated. This was confirmed by histopathological investigations. It was hypothesized that MSCs transplantation was superior over digoxin treatment regimen in improving heart function.